Experimental evidence from our laboratory and from others indicates that arginine vasopressin (AVP) possesses vasodilatory properties in a number of vascular beds. These data suggest that vasodilation is likely mediated by separate mechanisms in the systemic vs the pulmonary circulations, although definitive experiments have yet to be performed. The systemic vasodilatory effects of AVP appear to act mainly to modulate the potent vasoconstrictor properties of the peptide and likely are mediated by activation of V2- or V2-like vasopressinergic receptors. In contrast, the pulmonary circulation of certain species vasodilates in response to AVP and this vasodilation may be associated with V1-receptor activation although conflicting data exist regarding the receptor type responsible. The goal of the present application is to determine the mechanism for both systemic and pulmonary vasopressinergic vasodilation in the rat. Since pilot data suggest two separate mechanisms, the specific aims are organized into two sections focusing first on the pulmonary bed and then on the systemic circulation. Additional pilot data indicate a likely involvement of endothelial factors in these responses. The specific goals of the proposal are: SECTION I - Pulmonary Vasodilation Specific Aim #1 - Determine the receptor type(s) responsible for vasopressinergic pulmonary vasodilation. Specific #2 - Determine the role of endothelium-derived relaxing factor (EDRF) in the pulmonary response to AVP. Specific #3 - Determine the cellular second messenger for AVP-induced pulmonary vasorelaxation. SECTION II - Systemic Vasodilation Specific #4 - Determine whether EDRF is responsible for systemic vasopressinergic vasodilation. Specific #5 - Determine the cellular second messenger for AVP-induced systemic vasorelaxation. SECTION III - Physiological Relevance Specific #6 - Establish the physiological relevance of vasopressinergic vasodilation. Experiments in this proposal will investigate the cellular mechanisms responsible for vasopressinergic vasodilation in the pulmonary and systemic vasculatures. Both in vivo and in vitro techniques will be employed to determine both mechanisms and the physiological relevance of these actions of AVP on the conscious animal. Our findings will provide information concerning the mechanism by which AVP affects the circulation and thus have relevance to the many pathological situations associated with elevations in circulating levels of the peptide.